Aromatase inhibitors

High-yield Verified · Oct 2026

Prototype: anastrozole

Aromatase inhibitors are a class of medications used for anastrozole.

Medical view → mechanisms, drug comparisons and Step 1 pharmacology

Cut off estrogen at its main source after menopause. The price is paid in bone and joints.

How it works in the body

The system involved, what goes wrong, and how the drug and body interact.

01 Where estrogen comes from after menopause

Some breast cancers grow in response to estrogen. In postmenopausal women, estrogens come mainly from the aromatase enzyme, which converts adrenal androgens (androstenedione and testosterone) to estrone and estradiol. This conversion happens in peripheral tissues — the adrenal glands, skin, muscle and adipose tissue — and breast cancer cells have aromatase activity too, a possible local estrogen source for the tumor.

Blocking aromatase therefore lowers estrogen in the blood and in the tumor, which slows estrogen-driven growth of hormone receptor-positive breast cancer. It does not touch the adrenal glands’ other products: the labels report no meaningful effect on cortisol or aldosterone, so no corticosteroid replacement is needed.

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After menopause, peripheral aromatase is the main estrogen source — and the drug target.

02 Two ways to block the enzyme

Anastrozole and letrozole are nonsteroidal inhibitors. They bind aromatase noncovalently and can be displaced — letrozole competes for the heme of the enzyme’s cytochrome P450 subunit. Their names share the stem -rozole.

Exemestane is a steroidal inactivator, built like the natural substrate androstenedione. The enzyme processes it as a false substrate into an intermediate that binds irreversibly to its active site — “suicide inhibition.” Its stem is -mestane.

03 Why postmenopausal women

Before menopause the ovary is the main source of estrogen, and aromatization of adrenal androgens is not a significant source of estradiol, so anastrozole would not be expected to lower estradiol in premenopausal women. In premenopausal women, aromatase inhibitors increase gonadotropin secretion through reduced estrogen negative feedback on the pituitary, which stimulates the ovary.

Each breast cancer indication is labeled for postmenopausal women, and the exemestane label states that it is not indicated for breast cancer in premenopausal women. The same ovarian stimulation explains an off-label use: clinicians may use aromatase inhibitors to induce ovulation in the treatment of infertility.

04 The cost of low estrogen: bone, joints and lipids

Because these drugs lower circulating estrogen, they reduce bone mineral density and raise the risk of osteoporosis and fractures; bone loss can be seen within the first 6 months. The labels advise considering bone mineral density monitoring, and in a trial of anastrozole a bisphosphonate preserved bone density in most patients at risk of fracture (see the Bisphosphonates page).

Arthralgia — aromatase inhibitor–associated arthralgia syndrome — is the most common reason patients stop therapy. Joint pain, arthritis, carpal tunnel syndrome and tendon disorders including trigger finger are labeled. Total cholesterol can rise with anastrozole and letrozole, while exemestane lowered HDL cholesterol in a trial.

Drug names

Generic Brand

anastrozole Arimidex

letrozole Femara

exemestane Aromasin

Indications

Anastrozole (Arimidex) — adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer; first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer; treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy
Letrozole (Femara) — adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer; extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy; first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer; treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy
Exemestane (Aromasin) — adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to exemestane to complete five consecutive years of adjuvant hormonal therapy; treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy

Mechanism of action

Aromatase converts androgens (androstenedione and testosterone) to estrogens (estrone and estradiol); in postmenopausal women this peripheral conversion is the main estrogen source. Anastrozole and letrozole are selective nonsteroidal inhibitors that bind noncovalently and can be displaced (letrozole, a reversible inhibitor, binds competitively to the heme of the enzyme’s cytochrome P450 subunit). Exemestane is a steroidal false substrate that binds irreversibly to the active site and inactivates the enzyme. All three lower serum estradiol without meaningful effect on adrenal corticosteroid or aldosterone synthesis.

In plain terms

After menopause, the body still makes some estrogen by converting male-type hormones in fat and other tissues. These drugs shut down the enzyme that does the converting, starving estrogen-fed breast cancers.

Therapeutic effects — what you'll see working

Success is lower estrogen and control of hormone receptor-positive breast cancer, sustained over years of treatment — which depends on managing the bone loss and joint pain that make patients stop.

Estrogen suppression Breast cancer control

Estrogen suppression: Letrozole lowers serum estrone, estradiol and estrone sulfate; exemestane lowers circulating estrogens in postmenopausal women.
Breast cancer control: Lowering estrogen reduces estrogen-driven proliferation of hormone receptor-positive breast cancer cells.

Adverse effects

Their adverse effects are those of estrogen deprivation: hot flashes, bone loss, joint pain and vaginal dryness. Compared with tamoxifen, anastrozole caused fewer hot flashes, less vaginal bleeding, less endometrial cancer and fewer venous clots.

Bone loss and fractures Hold & notify

All three can decrease bone mineral density; fractures were more common with anastrozole and letrozole than with tamoxifen, and so was osteoporosis with letrozole.

Lower estrogen reduces bone mineral content and strength, which raises fracture risk. The labels advise considering bone mineral density monitoring; women on exemestane with or at risk of osteoporosis have it assessed by densitometry at the start.

Ischemic cardiovascular events (anastrozole) Report immediately

In women with pre-existing ischemic heart disease, ischemic cardiovascular events were more frequent with anastrozole than with tamoxifen.

Patients with ischemic heart disease are told to seek medical attention right away for new or worsening chest pain or shortness of breath.

Embryo-fetal toxicity Hold & notify

All three can cause fetal harm; letrozole is contraindicated in pregnancy.

Letrozole in pregnancy has resulted in spontaneous abortions and congenital birth defects. Females of reproductive potential use effective contraception during treatment and after the last dose, and have a pregnancy test before letrozole or exemestane is started.

Allergic, skin and liver reactions Report immediately

Angioedema, urticaria and anaphylaxis have been reported, as have severe skin reactions and hepatitis.

Swelling of the face, lips, tongue or throat can make swallowing or breathing difficult and needs immediate medical attention. Anastrozole has been linked to Stevens-Johnson syndrome and letrozole to toxic epidermal necrolysis.

Joint pain, carpal tunnel and tendon disorders Expected

Arthralgia and arthritis are common; carpal tunnel syndrome and tendon disorders, including trigger finger and tendon rupture, are labeled.

Aromatase inhibitor–associated arthralgia is the most common reason for discontinuation. Patients on anastrozole report tingling or numbness to their provider.

Hot flashes and estrogen-deprivation effects Expected

Hot flashes are among the most common adverse reactions; fatigue, headache, insomnia and sweating are also common.

Vaginal dryness, dyspareunia and sexual dysfunction occur. Letrozole can cause fatigue, dizziness and somnolence, so caution is advised when driving or using machinery.

Cholesterol Expected

Total cholesterol may rise with anastrozole and letrozole; the labels advise considering cholesterol monitoring.

In an exemestane trial, HDL cholesterol fell slightly while total and LDL cholesterol were unchanged.

Interactions

Anastrozole + tamoxifen drug

Do not combine — tamoxifen lowers anastrozole levels and the combination added no benefit over tamoxifen alone.

Letrozole + tamoxifen drug

Given together, tamoxifen lowers letrozole levels; letrozole still works when started immediately after tamoxifen.

Anastrozole or exemestane + estrogen-containing therapies drug

Estrogen may diminish or interfere with the aromatase inhibitor’s action — not used together.

Exemestane + strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort) drug

Exemestane exposure falls significantly; a dose increase is recommended with a strong inducer.

Exemestane + a high-fat meal food

Absorption rises; exemestane is taken after a meal.

Contraindications

The labeled contraindications are short — hypersensitivity for all three, plus pregnancy for letrozole. The other cautions come from what the drugs do: they harm a fetus, need a postmenopausal patient, and estrogen-containing therapies may diminish their action.

Any aromatase inhibitor — hypersensitivity to the drug or its excipients

Labeled contraindication; reactions include anaphylaxis, angioedema and urticaria.

Letrozole — pregnancy

Labeled contraindication — letrozole can cause fetal harm.

Anastrozole or exemestane — pregnancy use caution

A warning rather than a listed contraindication: both can cause fetal harm, so effective contraception is advised.

Exemestane — premenopausal women use caution

Not indicated for breast cancer in premenopausal women, whose main estrogen source is the ovary.

Estrogen-containing therapies with anastrozole or exemestane use caution

They should not be used together — estrogen may diminish the aromatase inhibitor’s action.

Anastrozole — pre-existing ischemic heart disease use caution

Ischemic cardiovascular events were more frequent; the label says to consider risks and benefits.

Letrozole — cirrhosis and severe hepatic impairment use caution

Exposure is about doubled, so a dose reduction is recommended.

When to hold

Assess before giving — these findings mean hold the dose and act.

Swelling of the face, lips, tongue or throat, or trouble swallowing or breathing

Seek emergency care — angioedema can obstruct the airway.

New or worsening chest pain or shortness of breath on anastrozole

Seek medical attention immediately — ischemic events were more frequent in women with heart disease.

Known or suspected pregnancy

Notify the prescriber — these drugs can cause fetal harm.

Tingling or numbness in the hands on anastrozole

Notify the provider — carpal tunnel syndrome is more common with anastrozole.

Labs & levels

Test Therapeutic / normal Toxic / critical

Bone mineral density (DXA) At baseline before treatment, then periodically during therapy — —

25-hydroxy vitamin D Before starting an aromatase inhibitor (exemestane label); supplement if deficient — —

Serum cholesterol / lipid profile At baseline and during therapy — —

Liver function tests and blood count At baseline before treatment — —

Pregnancy test (females of reproductive potential) Before starting letrozole; within 7 days before starting exemestane — —

Nursing considerations

The RN-specific layer — each action paired with the reason it matters.

Bone health

Make sure a baseline bone density scan is done and repeated as ordered, and check a vitamin D level before an aromatase inhibitor is started.

Why: These drugs lower estrogen and bone mineral density, and vitamin D deficiency is common in women with early breast cancer.

Teach adequate calcium and vitamin D intake and weight-bearing exercise, and report any bone pain or fracture.

Why: Bone loss raises the risk of osteoporosis and fractures; bone-protective therapy may be added when indicated.

Adherence and symptoms

Ask about joint pain, stiffness, hand tingling or numbness, and hot flashes at each visit, and report them rather than letting the patient stop the drug.

Why: Arthralgia is the most common reason for discontinuation, and switching to another aromatase inhibitor may relieve intolerable effects.

Teach adherence for the whole course; a missed anastrozole dose is taken when remembered unless the next dose is near, and two doses are never taken together.

Why: Adjuvant treatment runs for years — five in the anastrozole adjuvant trial — and the label gives these missed-dose instructions.

Give exemestane after a meal; anastrozole and letrozole can be taken with or without food.

Why: The labels specify these administration conditions.

Warn patients on letrozole about fatigue and dizziness before driving or using machinery.

Why: Fatigue, dizziness and somnolence have been reported.

Reproductive safety

For females of reproductive potential, confirm a negative pregnancy test before letrozole or exemestane and teach effective contraception during treatment and after the last dose.

Why: All three can cause fetal harm, and letrozole is contraindicated in pregnancy.

Advise not breastfeeding during treatment and for the period after the last dose that each label specifies.

Why: Serious adverse reactions in a breastfed infant are possible.

Medication review

Check the list for tamoxifen with anastrozole, and for estrogen-containing products with anastrozole or exemestane.

Why: Tamoxifen is not given with anastrozole, and estrogens counteract the aromatase inhibitor.

With exemestane, ask about rifampicin, anticonvulsants or St. John’s wort.

Why: Strong CYP3A4 inducers significantly lower exemestane exposure.

Teach the patient to seek immediate care for facial, lip, tongue or throat swelling, and — with heart disease on anastrozole — for new chest pain or breathlessness.

Why: Angioedema and ischemic cardiovascular events are labeled risks.

Common questions

What are Aromatase inhibitors used for?

Anastrozole (Arimidex) for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. Letrozole (Femara) for adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. Exemestane (Aromasin) for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to exemestane to complete five consecutive years of adjuvant hormonal therapy.

How do Aromatase inhibitors work?

What are the serious side effects of Aromatase inhibitors?

Watch for all three can decrease bone mineral density; fractures were more common with anastrozole and letrozole than with tamoxifen, and so was osteoporosis with letrozole; in women with pre-existing ischemic heart disease, ischemic cardiovascular events were more frequent with anastrozole than with tamoxifen; all three can cause fetal harm; letrozole is contraindicated in pregnancy.

When should a nurse hold Aromatase inhibitors, and what safety checks apply?

Swelling of the face, lips, tongue or throat, or trouble swallowing or breathing: seek emergency care — angioedema can obstruct the airway. New or worsening chest pain or shortness of breath on anastrozole: seek medical attention immediately — ischemic events were more frequent in women with heart disease. Known or suspected pregnancy: notify the prescriber — these drugs can cause fetal harm. Tingling or numbness in the hands on anastrozole: notify the provider — carpal tunnel syndrome is more common with anastrozole.

What labs should be monitored with Aromatase inhibitors?

Monitor bone mineral density (DXA), 25-hydroxy vitamin D, serum cholesterol / lipid profile, liver function tests and blood count, and pregnancy test (females of reproductive potential).

Sources

Reviewed by Hae Suk Lee, RN

Educational summary for nursing students. Always verify against current prescribing information and your institution's protocols before administering. Not medical advice.